The proposed work aims to analyze both genetic and environmental factors which are pathogenetically involved in human obesity. In these studies obesity will be defined as adiposity and will be further analyzed in terms of hypertrophy (enlargement of adipocytes) and hyperplasia (increased number of adipocytes) of adipose tissue. Furthermore, the morphology of adipose tissue will be related to its metabolic function in vitro and to various metabolic abnormalities associated with excessive adiposity in vivo. The performance of these studies both on the obese propositi and all their first degree relatives will lead to a better understanding of the genetics of human obesity. In addition, the study of people before, during and after the development of excessive adiposity will provide a picture of human obesity as an evolving process and will enhance our understanding of its relationship to carbohydrate intolerance, insulin resistance, hypertriglyceridemia as well as insulin and growth hormone secretion.